ADHD: Child. Gail A. Mattox, MD, FAACAP Morehouse School of Medicine Russell E. Scheffer, MD University of Kansas School of Medicine- Wichita

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2 ADHD: Child Gail A. Mattox, MD, FAACAP Morehouse School of Medicine Russell E. Scheffer, MD University of Kansas School of Medicine- Wichita

3 Learning Objective Implement assessment tools for accurate diagnosis and develop an evidence-based treatment strategy to optimize the management of ADHD in children and adolescents

4 Recognizing ADHD in Children and Adolescents Gail A. Mattox, MD, FAACAP Morehouse School of Medicine

5 Gail A. Mattox, MD, FAACAP Disclosures Research/Grants: None Speakers Bureau: None Consultant: None Stockholder: None Other Financial Interest: None Advisory Board: None

6 Learning Objective Recognize the importance of early identification of symptoms for improved diagnosis and treatment of children and adolescents with ADHD

7 ADHD A Common Disorder

8 ADHD One of the most common psychiatric disorders of childhood A neurobiological disorder Results in significant impairment Most will continue to meet criteria during adolescence Frequently associated with comorbid disorders

9 Prevalence and Impact Common disorder, long-lasting 5 10% of children in United States 2.5x more frequently reported in males Disparities in access and treatment Cost of illness $36 52 billion More likely to have major injuries Greater risk for accidents Accessed July 8, 2009.

10 Core Symptoms Inattention Impulsivity Hyperactivity Accessed July 8, 2009.

11 ADHD Types ADHD Combined Type ADHD Predominantly Inattentive Type ADHD Predominantly Hyperactive/Impulsive Type Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

12 ADHD Core Symptoms Difficulty sustaining attention Does not seem to listen Makes careless mistakes Difficulty organizing tasks Easily distracted Often forgetful Often loses things Often does not follow through Difficulty playing quietly Fidgets, squirms Leaves seat Runs about Often on the go Often talks excessively Blurts out Often interrupts Can t wait turn Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

ADHD Presentation During Adolescence Risky, impulsive behavior Driving, drugs/alcohol, sex, risk-taking Gives up easily Difficulty organizing tasks, poor time management, and easily

13 ADHD Presentation During Adolescence Risky, impulsive behavior Driving, drugs/alcohol, sex, risk-taking Gives up easily Difficulty organizing tasks, poor time management, and easily distracted , IM/texting, jobs, sports Interrupts Fooling around behavior Annoys others Often in trouble, difficulty with authority Greenhill L. J Clin Psychiatry 1998;5(suppl 7):31-41.

ADHD Diagnostic Criteria DSM-IV-TR Usually appears early between 3 6 must have impairment before age 7 Impairment in two or more settings Clinically significant impairment x 6 mos Must exclude other

14 ADHD Diagnostic Criteria DSM-IV-TR Usually appears early between 3 6 must have impairment before age 7 Impairment in two or more settings Clinically significant impairment x 6 mos Must exclude other disorders 6 or more symptoms of inattention or 6 or more symptoms of hyperactivity or impulsivity Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000.

15 State-Based Prevalence of ADHD Diagnosis Accessed July 8, 2009.

16 Correlates of ADHD Low self-esteem Impaired peer relationships Lower academic achievement School failure Family difficulties

17 ADHD Assessment Parent Interview ADHD symptoms Impairment Comorbidity Academic function Family history Medical and developmental history Behavior Rating Scales Parent Teacher Child Interview ADHD symptoms? Inconsistencies Mental status exam Neuropsychological Testing Academic impairment Learning disabilities Executive function optional Laboratory/ Neurological Testing Only if strong evidence in medical history Pliszka S, et al. J Am Acad Child Adolesc Psychiatry 2007;46:

AACAP Practice Guidelines Recommendations Unremarkable medical history laboratory and neurological testing is not indicated Psychological

18 AACAP Practice Guidelines Recommendations Unremarkable medical history laboratory and neurological testing is not indicated Psychological and neuropsychological are not mandatory Neuroimaging a research tool Pliszka S, et al. J Am Acad Child Adolesc Psychiatry 2007;46:

19 Behavior Rating Scales for ADHD Recommended Academic Performance Rating Scale ADHD Rating Scale IV Child Behavior Checklist Conners Parent Rating Scale Conners Teacher Rating Scale Conners Wells Adolescent Self Report Scale Vanderbilt ADHD Diagnostic Parent and Teacher Scales

20 Resources for Rating Scales National Resource Center on ADHD American Academy of Pediatrics American Academy of Child and Adolescent Psychiatry Bright Futures bridges/adhd.pdf

21 ADHD and Comorbidity Look for comorbidities in patients with ADHD Offer appropriate treatment options for both ADHD and comorbidities

22 Common Comorbidities Prevalence with ADHD Disruptive Behavior Disorders ODD, CD Anxiety Disorders ODD, 39.9% CD, 14.3% 33.5% ADHD Mania/Hypomania 2.2% 22% Affective Disorder MTA Cooperative Group. Arch Gen Psychiatry 1999;56:

23 Summary ADHD is a common childhood disorder with negative impact on multiple areas of function High prevalence of continuation of disorder into adolescence with varying presentations Assessment and diagnosis requires multipronged approach Psychiatric comorbidities prevalent

24 Intervention Strategies Are Effective

25 Treatment Strategies for Childhood ADHD Russell E. Scheffer, MD University of Kansas School of Medicine-Wichita

26 Russell E. Scheffer, MD Disclosures Research/Grants: Wyeth Pharmaceuticals Speakers Bureau: None Consultant: AstraZeneca Pharmaceuticals LP Stockholder: None Other Financial Interest: None Advisory Board: None

27 Learning Objective Compare and contrast the current treatment options for ADHD and develop individualized management strategies for each patient

28 Treatment Overview Why Treat It? Myths and Legends Mechanisms of Action Drug Delivery System Treatment Choices Optimizing Treatment Sculpting Side Effects Concurrent Conditions

ADHD: Impact of Untreated & Under-Treated ADHD Health Care System 50% in bike accidents 1 33% in ER visits 2 2-4x more motor vehicle crashes 3-5 Patient Family 3-5x parental divorce or separation

29 ADHD: Impact of Untreated & Under-Treated ADHD Health Care System 50% in bike accidents 1 33% in ER visits 2 2-4x more motor vehicle crashes 3-5 Patient Family 3-5x parental divorce or separation 10,11 2-4x sibling fights 12 School & Occupation 46% expelled 6 35% drop out 6 Lower occupational status 7 Society Substance use disorders: 2x risk 8 Earlier onset 8 Less likely to quit smoking in adulthood 9 Employer parental absenteeism 13 and productivity 13 See supplemental bibliography for a complete list of references.

30 Concerns About Drug Abuse Stimulants are Schedule II and should be taken seriously and monitored closely You do not get sued less because you did not see the patient Addictive potential is based upon rapid onset (absorption) and euphoric effects Diversion mostly for amateurs and college students Tactics to change schedule Prodrug Getting rid of the L isomer (early peak onset)

31 Substance Abuse in ADHD Youth Growing Up Overall Rate of Substance Abuse (n = 19) (n = 56) (n = 137) Odds Ratio = 6.3; p <.001 Biederman J, et al. Pediatrics 1999;104:e20.

32 Synaptic Actions of ADHD Medications Presynaptic vesicle + release DA Reuptake Atomoxetine Blocks NE reuptake Some DA reuptake NE Reuptake D-Amphetamine Blocks reuptake of DA and NE Increases recirculating pools Methylphenidate Blocks reuptake of DA

33 Drug Delivery Systems It s Really What Differentiates the Meds Immediate-release Sustained-release Beads (bid dosing in one capsule) OROS (ascending profile sipping studies) Methylphenidate transdermal patches Prodrug lisdexamfetamine dimesylate effective 13 hours post-dose

34 Effect Sizes for FDA-Approved ADHD Medications Effect Size Represents the mean effect size for each class of medication -1 Non-Stimulant Immediate-Release Stimulants Long-Acting Stimulants p <.05 for stimulants vs. non-stimulants Faraone SV, et al. Medscape General Medicine 2006;8:4. Available at:

35 Recommended Medications for ADHD Medication* Methylphenidate Ritalin, Methylin Concerta Metadate ER, Metadate CD, Methylin ER Ritalin LA Focalin Daytrana Initial Dose mg Usual Dose Doses per Day Side Effects Appetite suppression, stomachaches, headaches, irritability, weight loss, deceleration in rate of growth, exacerbation of psychosis, exacerbation of tics, mild increase in blood pressure and pulse Contraindications Marked anxiety, tension, agitation, glaucoma, use of monoamine oxidase inhibitors, seizures, tics * For each category the generic drug is given and dosing information for each named marketed drug. The manufacturer states that seizures and tic disorder are contraindications; research supports the use of stimulants in children with seizures that have stabilized with the use of anticonvulsants and in children with tic disorder or Tourette s disorder. With use of long-acting methylphenidate or dextroamphetamine product, a short-acting product may be added at 4 p.m. to 6 p.m. for homework or special activities; appetite and sleep onset are then carefully monitored. Focalin is a dextro isomer of methylphenidate that is given at a lower level.

36 Recommended Medications for ADHD Medication* Dexedrine Dexedrine Spansule Adderall Addreall XR Initial Dose mg Usual Dose Doses per Day Dextroamphetamine (sulfate alone and in combination with amphetamine salts) Side Effects Appetite suppression, stomachaches, headaches, irritability, weight loss, possible growth inhibition, exacerbation of psychosis, exacerbation of tics, mild increase in blood pressure and pulse Contraindications Cardiovascular disease, hypertension, hyperthyroidism, glaucoma, drug dependence, use of monoamine oxidase inhibitors * For each category the generic drug is given and dosing information for each named marketed drug. The manufacturer states that seizures and tic disorder are contraindications; research supports the use of stimulants in children with seizures that have stabilized with the use of anticonvulsants and in children with tic disorder or Tourette s disorder. With use of longacting methylphenidate or dextroamphetamine product, a short-acting product may be added at 4 p.m. to 6 p.m. for homework or special activities; appetite and sleep onset are then carefully monitored.

37 Recommended Medications for ADHD Medication* Initial Dose Usual Dose Doses per Day Side Effects Contraindications mg Lisdexamfetamine dimesylate (LDX) Vyvanse Vomiting, nausea, dry mouth, upper abdominal pain, pyrexia, Insomnia, irritability, appetite suppression, irritability, weight loss, possible growth inhibition, exacerbation of psychosis, dizziness, somnolence, exacerbation of tics, mild increase in blood pressure and pulse Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to serve hypertension, hyperthyroidism, known hypersensitivity or idiosyncratic reaction to sympathomimetic amines, glaucoma, history of drug abuse, use of monoamine oxidase inhibitors For each category the generic drug is given and dosing information for each named marketed drug.

Recommended Medications for ADHD Medication Initial Dose Usual Dose Doses per Day Side Effects Contraindications mg Atomoxetine ƒ Strattera 10-25 18-60 1 Appetite suppression, nausea, vomiting,

38 Recommended Medications for ADHD Medication Initial Dose Usual Dose Doses per Day Side Effects Contraindications mg Atomoxetine ƒ Strattera Appetite suppression, nausea, vomiting, fatigue, weight loss, deceleration in rate of growth, mild increase in blood pressure and pulse Jaundice or other clinical or laboratory evidence of liver injury, use of monoamine oxidase inhibitors, narrowangle glaucoma Bupropion Wellbutrin SR Wellbutrin XL Weight loss, insomnia, agitation, anxiety, dry mouth, seizures, others Seizures, bulimia, anorexia nervosa, abrupt discontinuation of alcohol or benzodiazepines, use of monoamine oxidase inhibitors or other bupropion products (e.g., Zyban) * For each category the generic drug is given and dosing information for each named marketed drug. ƒ Younger children may need two doses a day. Bupropion has not been approved by the FDA for pediatric use. Only sustained release (twice daily) or extended release (once daily) are recommended for adolescents. There is a higher incidence of side effects with the immediate-release preparation.

Percent Normalized at 14-Month Endpoint Across the Four MTA Groups 88% 68% NS 56% 34% NS 25% The classroom controls were drawn from the same classroom cohorts as MTA children were originally, and

39 Percent Normalized at 14-Month Endpoint Across the Four MTA Groups 88% 68% NS 56% 34% NS 25% The classroom controls were drawn from the same classroom cohorts as MTA children were originally, and were age- and gender-matched to assure comparability with MTA subjects. The normalization indicator was based on a composite of parent and teacher ratings, with the overall symptom cutoff required to be indicative of little or no symptoms). Swanson JM, et al. J Am Acad Child Adolesc Psychiatry 2001;40:

Sculpting Optimizing Treatments Goals: Good coverage throughout the day (or when needed) Avoid or fill excessive troughs How do you know if this is the best they

40 Sculpting Optimizing Treatments Goals: Good coverage throughout the day (or when needed) Avoid or fill excessive troughs How do you know if this is the best they can be? Switches can improve or worsen MPH vs. damph Optimal dosing frequently we stop when they are better with little idea of what they could be Other treatments

41 Sculpting Solutions Problem Solution 1 Solution 2 Lack of early morning efficacy Can not get ready in the a.m. Does not last long enough Trouble settling for bed Wakes up late on weekends Add an IR dose to the XR Take meds 1 hour before desired wake up time Add an IR dose later Clonidine or guanfacine Consider a patch Possibly atomoxetine Take an IR dose upon awakening Add a second XR dose or atomoxetine HS dose of IR stimulant Use IR instead

42 Side Effects GI distress Vomiting Nausea Dry mouth Irritability Tics Insomnia Affective lability Decreased appetite (anorexia) Increased pulse Increased blood pressure

43 Wear Off and Rebound Stimulants are out of the blood stream every day Irritability and moodiness can occur as the meds are wearing off Poor settling for bed is frequently a characteristic of patients with ADHD even before treatment it becomes a focus when everything else is better Alpha2 adrenergic agonists can improve this

44 Non-Stimulants Atomoxetine Alpha2 adrenergic agonists Bupropion Tricyclic antidepressant

45 ADHD Comorbidity Conduct disorder Oppositional defiant disorder Tic disorders Sleep problems: Failure to settle accelerate at bedtime Depression Anxiety disorders Bipolar disorder Tourette s disorder Learning disorders

Treatment of Concurrent Conditions Condition Solution 1 Solution 2 Aggression Anxiety disorder Depression Alpha2 adrenergic agonist Start low and go slow with stimulant Treat ADHD first, if still

46 Treatment of Concurrent Conditions Condition Solution 1 Solution 2 Aggression Anxiety disorder Depression Alpha2 adrenergic agonist Start low and go slow with stimulant Treat ADHD first, if still present SSRI Antipsychotic or mood stabilizer Treat the anxiety disorder or atomoxetine Consider bupropion Tic disorder Lower dose Alpha2 adrenergic agonist Bipolar disorder Treat BPD first Consider over stabilization Learning disorder Treat ADHD Refer to learning specialist Conduct/ODD Treat ADHD Consider Alpha2 agonist, antipsychotic later Behavioral interventions should be considered at each step for disruptive behavior disorders.

47 Why Consider Non-Pharmacological Treatment for ADHD? Medication does not ameliorate existing skills deficits 1 Deficits in prosocial skills remain Academic achievement does not improve Some children only partial responders 2 Poor maintenance effects after withdrawal of medication 3 No appreciable impact on long-term outcome 3 1. Loe IM, Feldman HM. Ambul Pediatr 2007: MTA Cooperative Group. Arch Gen Psychiatry 1999;56: Jensen PS, et al. J Am Acad Child Adolesc Psychiatry 2007;46:

48 Why Consider Non-Pharmacological Treatment for ADHD? Patient preferences and satisfaction Some individuals unable to tolerate side effects of medications Added benefits of combining pharmacologic and psychosocial treatments 1,2,3 May improve broader outcomes May be necessary for some individuals to achieve significant improvement May lower the acute and lifetime dosages of medication 1. Conners CK, et al. J Am Acad Child Adolesc Psychiatry 2001;40: MTA Cooperative Group. Arch Gen Psychiatry 1999;56: Vitielo B, et al. J Am Acad Child Adolesc Psychiatry 2001;40:

49 Summary Individualize treatment strategies for each patient based on safety, efficacy, and tolerability of treatment options Drug delivery systems matter Sculpting is an important option for optimizing treatment Consider comorbid psychiatric disorders in management strategy

50 an educational series offered by CME Outfitters, LLC This CME/CE activity is co-sponsored by

51 Recognizing ADHD in Children and Adolescents Gail A. Mattox, MD, FAACAP Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV-TR). Washington, DC: American Psychiatric Association, Greenhill LL. Diagnosing attention-deficit/hyperactivity disorder in children. J Clin Psychiatry 1998;59(Suppl 7): Accessed July 8, MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. The MTA Cooperative Group multimodal treatment study of children with ADHD. Arch Gen Psychiatry 1999;56: Pliszka S; AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2007;46:

52 Treatment Strategies for Childhood ADHD Russell E. Scheffer, MD Barkley R, Fischer M, Edelbrock C, et al. The adolescent outcome of hyperactive children diagnosed by research criteria--iii. Mother-child interactions, family conflicts and maternal psychopathology. J Child Psychol Psychiatry 1991;32: Barkley R, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993;92: Barkley R, Murphy KR, Kwasnik D. Motor vehicle driving competencies and risks in teens and young adults with attention deficit hyperactivity disorder. Pediatrics 1996;98: Biederman J, Wilens T, Mick E, et al. Pharmacotherapy of attention-deficit/hyperactivity disorder reduces risk for substance use disorder. Pediatrics 1999;104:e20. Brown RT, Pacin JN. Perceived family functioning, marital status, and depression in parents of boys with attention deficit disorder. J Learn Disabil 1989;22: Conners CK, Epstein JN, March JS, et al. Multimodal treatment of ADHD in the MTA: an alternative outcome analysis. J Am Acad Child Adolesc Psychiatry 2001;40: DiScala C, Lescohier I, Barthel M, Li G. Injuries to children with attention deficit hyperactivity disorder. Pediatrics 1998;102:14, Faraone SV, Biederman J, Spencer TJ, Aleardi M. Comparing the efficacy of medications for ADHD using metaanalysis. MedGenMed 2006;8:4. Fischer M, Barkley R, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58: Jensen PS, Arnold LE, Swanson JM, et al. 3-year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry 2007;46: Leibson CL, Barbaresi WJ, Ransom J, et al. Emergency department use and costs for youth with attentiondeficit/hyperactivity disorder: associations with stimulant treatment. Ambul Pediatr. 2006;6: Loe IM, Feldman HM. Academic and educational outcomes of children with ADHD. Ambul Pediatr 2007;7(Suppl 1): Mannuzza S, Klein RG, Bessler A, et al. Educational and occupational outcome of hyperactive boys grown up. J Am Acad Child Adolesc Psychiatry 1997;36: Mash EJ, Johnston C. Parental perceptions of child behavior problems, parenting self-esteem, and mothers' reported stress in younger and older hyperactive and normal children. J Consult Clin Psychol 1983;51: MTA Cooperative Group. Multimodal treatment study of children with ADHD. Arch Gen Psychiatry 1999;56: Noe L, Hankin CS. Health outcomes of childhood attention-deficit/hyperactivity disorder (ADHD): health care use and work status of caregivers. Value in Health 2001;4: NHTSA. Available at: Pomerleau OF, Downey KK, Stelson FW, et al. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse 1995;7: Swanson JM, Kraemer HC, Hinshaw SP, et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of ADH and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry 2001;40: Vitiello B, Severe JB, Greenhill LL, et al. Methylphenidate dosage for children with ADHD over time under controlled conditions: lessons from the MTA. J Am Acad Child Adolesc Psychiatry 2001;40: Wilens T, Biederman J, Mick E, et al. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185:

53 Supplemental Bibliography for: Treatment Strategies for Childhood ADHD Russell E. Scheffer, MD Slide Title: ADHD: Impact of Untreated & Under-Treated ADHD 1. DiScala C, Lescohier I, Barthel M, Li G. Injuries to children with attention deficit hyperactivity disorder. Pediatrics 1998;102:14, Leibson CL, Barbaresi WJ, Ransom J, et al. Emergency department use and costs for youth with attention-deficit/hyperactivity disorder: associations with stimulant treatment. Ambul Pediatr 2006;6: NHTSA. Available at: 4. Barkley R, Guevremont DC, Anastopoulos AD, et al. Driving-related risks and outcomes of attention deficit hyperactivity disorder in adolescents and young adults: a 3- to 5-year follow-up survey. Pediatrics 1993;92: Barkely R, Murphy KR, Kwasnik D. Motor vehicle driving competencies and risks in teens and young adults with attention deficit hyperactivity disorder. Pediatrics 1996;98: Fischer M, Barkley R, Edelbrock CS, et al. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58: Mannuzza S, Klein RG, Bessler A, et al. Educational and occupational outcome of hyperactive boys grown up. J Am Acad Child Adolesc Psychiatry 1997;36: Wilens T, Biederman J, Mick E, et al. Attention deficit hyperactivity disorder (ADHD) is associated with early onset substance use disorders. J Nerv Ment Dis 1997;185: Pomerleau OF, Downey KK, Stelson FW, et al. Cigarette smoking in adult patients diagnosed with attention deficit hyperactivity disorder. J Subst Abuse 1995;7: Barkley R, Fischer M, Edelbrock C, et al. The adolescent outcome of hyperactive children diagnosed by research criteria--iii. Mother-child interactions, family conflicts and maternal psychopathology. J Child Psychol Psychiatry 1991;32: Brown RT, Pacin JN. Perceived family functioning, marital status, and depression in parents of boys with attention deficit disorder. J Learn Disabil 1989;22: Mash EJ, Johnston C. Parental perceptions of child behavior problems, parenting self-esteem, and mothers' reported stress in younger and older hyperactive and normal children. J Consult Clin Psychol 1983;51: Noe L, Hankin CS. Health outcomes of childhood attention-deficit/hyperactivity disorder (ADHD): health care use and work status of caregivers. Value in Health 2001;4:

The Use of ADHD Medication in the Pediatric Population

The Use of ADHD Medication in the Pediatric Population Shirin Madzhidova, PharmD Pediatric Pharmacotherapy Fellow Nova Southeastern University Objectives Discuss the importance of treatment with medications